Potentiation of the protective effect of hypercapnic hypoxia in combination with pharmacological neuroprotective agents

Abstract

Aim. We studied the possibility of potentiating the neuroprotective effect of hypercapnic hypoxia using a combination with pharmacological activators of major mechanisms that increase the brain tolerance to ischemia/hypoxia. Methods. Studies were carried out on 140 male Wistar rats conditioned with respiratory hypercapnic hypoxia (P_O2 – 90 mm Hg; P_CO2 – 50 mm Hg) for 5 days, 30 min daily. After this exposure, the rats were injected with a drug (adenosine receptor activator (ATP), carbonic anhydrase blocker (acetazolamide), opioid receptor activator (dalargin), angiotensin converting enzyme (ACE) blocker (enalapril). 24 hrs later, the common carotid arteries were occluded bilaterally. 72 hrs after drug injection, the damaged/surviving cells in the CA1 region of the hippocampus were counted. Results. Morphological evaluation of neuronal survival showed that enalapril enhanced the neuroprotective effect of hypercapnic hypoxia. ATP and dalargin did not significantly increase this effect, and acetazolamide completely eliminated this neuroprotective effect. Conclusion. Thus, the neuroprotective effect of hypercapnic hypoxia conditioning was potentiated by its combination with an ACE inhibitor.